These studies are designed to investigate the role of heme in the regulation of the biosynthesis, assembly, and functional activation of hepatic hemoproteins during mammalian development. A functional association between heme synthesis and the biosynthesis of mitochondrial hemoproteins is suggested by the accelerated rate of both processes in fetal liver and the rapid decline in the rate of mitochondrial protein synthesis observed when heme synthesis is inhibited. Heme appears to stimulate new apocytochrome oxidase synthesis in the fetus and mediates the assembly of apoprotein and heme into a functional cytochrome. Prenatal exposure to agents which inhibit hepatic heme biosynthesis results in delayed or inhibited postnatal development of both mitochondrial and microsomal hemoprotein function. Thus, heme may be rate-limiting in the synthesis of both mitochondrial and microsomal hemoproteins during mammalian development.